• Proceedings of the Korean Society of Applied Pharmacology
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• 1998.11a
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• pp.126-126
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• 1998

Studies on natural products are of great interest, due to the limits in development of synthesized medicine and its side effects. Deer antler is the most popular cure-all type drug among Asian folk medicines. In this study, we newly isolated the biologically active components from chloroform extract and 70% ethanol extract of deer antler, and analyzed their structures. First, the structure of monoacetyldiglyceride in deer antler was identified. To investigate the structure-activity relationship of monoacetyldiglycerides, we synthesized diverse substituted glycerides from glycerol, and confirmed their structures by spectroscopic methods. Among seven structurally-interesting compounds tested in this study, compound 1,2,3,5, and 6 showed activity toward [Ca$\^$2+/]$\_$i/ increase in fura-2 loaded rat pancreatic acinar cells. Second, 70% ethanol extract of deer antler stimulated insulin release from rat pancreatic islets. We found the most effective fraction was CN-Es-8 in 70% ethanol extract, and it increased intracellular Ca$\^$2+/ concentration in pancreatic ${\beta}$-cell.

• Nutrition Research and Practice
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• v.15 no.3
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• pp.294-308
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• 2021

BACKGROUD/OBJECTIVES: Allomyrina dichotoma larva (ADL), one of the many edible insects recognized as future food resources, has a range of pharmacological activities. In a previous study, an ADL extract (ADLE) reduced the hepatic insulin resistance of high-fat diet (HFD)-induced diabetic mice. On the other hand, the associated molecular mechanisms underlying pancreatic beta-cell dysfunction remain unclear. This study examined the effects of ADLE on palmitate-induced lipotoxicity in a beta cell line of a rat origin, INS-1 cells. MATERIALS/METHODS: ADLE was administered to high-fat diet treated mice. The expression of apoptosis-related molecules was measured by Western blotting, and reactive oxidative stress generation and nitric oxide production were measured by DCH-DA fluorescence and a Griess assay, respectively. RESULTS: The administration of ADLE to HFD-induced diabetic mice reduced the hyperplasia, 4-hydroxynonenal levels, and the number of apoptotic cells while improving the insulin levels compared to the HFD group. Treatment of INS-1 cells with palmitate reduced insulin secretion, which was attenuated by the ADLE treatment. Furthermore, the ADLE treatment prevented palmitate-induced cell death in INS-1 cells and isolated islets by reducing the apoptotic signaling molecules, including cleaved caspase-3 and PARP, and the Bax/Bcl2 ratio. ADLE also reduced the levels of reactive oxygen species generation, lipid accumulation, and nitrite production in palmitate-treated INS-1 cells while increasing the ATP levels. This effect corresponded to the decreased expression of inducible nitric oxide synthase (iNOS) mRNA and protein. CONCLUSIONS: ADLE helps prevent lipotoxic beta-cell death in INS-1 cells and HFD-diabetic mice, suggesting that ADLE can be used to prevent or treat beta-cell damage in glucose intolerance during the development of diabetes.

• Journal of the Korean Applied Science and Technology
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• v.1 no.1
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• pp.37-47
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• 1984

Effects of garlic on hypocholesterolemia, anticoagulation and hypoglycemia were studied in the present experiments using male rats. The results were summarized as follows. 1. The supplementation of $2{\sim}4%$ garlic to 2% cholesterol diets did not affect food intake and weight gain in male rats. 2. Rat's groups fed the diets supplemented with $2{\sim}3%$ garlic (C.D.E.F) to 2% cholesterol diet (B) decreased serum total cholesterol levels by $16{\sim}32%$, triglyceride levels by $18.6{\sim}26.8%$ and ${\beta}/{\alpha}-lipoportein$ rations by $42{\sim}58%$, but increased HDL-cholesterol levels by $29{\sim}65%$ as compared to B group, and so the author assumes that garlic supplementation exerts hypocholesterolemic effect on cholesterol - fed rats because of the increase of HDL and HDL - cholesterol levels. 3. Rat's groups fed the diets supplemented with $2{\sim}4%$ garlic (C.D.E.F) to 2% cholesterol plus 0.25% bile salt diet (B) increased whole blood coagulation times, prothrombin times and fibrinolytic activities, but decreased plasma fibrinogen levels as compared to B group, and so the author assumes that garlic supplementation exerts anticoagulative effect because of the inhibition of fibrinogen synthesis in male rat's liver. 4. Rat's groups fed the diets supplemented with $2{\sim}4%$ garlic (B.C.D.E) to standard diet (A) decreased serum glucose levels by $1{\sim}24%$, but increased serum insulin concentrations by $0.5{\sim}3.0$ times as compared to A group, and so the author assumes that garlic supplementation exerts hypoglycemic effect because of the increase of serum insulin levels by stimulation pancreatic secretion of insulin from ${\beta}-cells$ in the islets of Langerhans.

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.1
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• pp.39-44
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• 2006

Type I diabetes (T1D) is an organ-specific autoimmune disease caused by the T cell-mediated destruction of the insulin-producing ${\beta}$ cells in the pancreatic islets. The onset of T1D is the consequence of a progressive destruction of islet ${\beta}$ cells mediated by an imbalance between effector $CD4^+$ T helper (Th)1 and regulatory $CD4^+$ Th2 cell function. Since interferon-alpha (IFN-${\alpha}$) has been known to modulate immune function and autoimmunity, we investigated whether administration of adenoviralmediated IFN-${\alpha}$ gene would inhibit the diabetic process in NOD mice. The development of diabetes was significantly inhibited by a single injection of adenoviral-mediated IFN-${\alpha}$ gene before 8 weeks of age. Next, we examined the hypothesis that Th2-type cytokines are associated with host protection against autoimmune diabetes, whereas Th1-type cytokines are associated with pathogenesis of T1D. The expression of IFN-${\alpha}$ induced increase of serum IL-4 and IL-6 (Th2 cytokines) levels and decrease of serum IL-12 and IFN-${\gamma}$ (Th1 cytokines) levels. Therefore, overexpression of IFN-${\alpha}$ by adenoviralmediated delivery provides modulation of pathogenic progression and protection of NOD mice from T1D.

• Asian-Australasian Journal of Animal Sciences
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• v.33 no.11
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• pp.1837-1847
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• 2020

Objective: To evaluate the pancreatic differentiation potential of α-1,3-galactosyltransferase knockout (GalTKO) pig-derived bone marrow-derived mesenchymal stem cells (BM-MSCs) using epigenetic modifiers with different pancreatic induction media. Methods: The BM-MSCs have been differentiated into pancreatic β-like cells by inducing the overexpression of key transcription regulatory factors or by exposure to specific soluble inducers/small molecules. In this study, we evaluated the pancreatic differentiation of GalTKO pig-derived BM-MSCs using epigenetic modifiers, 5-azacytidine (5-Aza) and valproic acid (VPA), and two types of pancreatic induction media - advanced Dulbecco's modified Eagle's medium (ADMEM)-based and N2B27-based media. GalTKO BM-MSCs were treated with pancreatic induction media and the expression of pancreas-islets-specific markers was evaluated by real-time quantitative polymerase chain reaction, Western blotting, and immunofluorescence. Morphological changes and changes in the 5'-C-phosphate-G-3' (CpG) island methylation patterns were also evaluated. Results: The expression of the pluripotent marker (POU class 5 homeobox 1 [OCT4]) was upregulated upon exposure to 5-Aza and/or VPA. GalTKO BM-MSCs showed increased expression of neurogenic differentiation 1 in the ADMEM-based (5-Aza) media, while the expression of NK6 homeobox 1 was elevated in cells induced with the N2B27-based (5-Aza) media. Moreover, the morphological transition and formation of islets-like cellular clusters were also prominent in the cells induced with the N2B27-based media with 5-Aza. The higher insulin expression revealed the augmented trans-differentiation ability of GalTKO BM-MSCs into pancreatic β-like cells in the N2B27-based media than in the ADMEM-based media. Conclusion: 5-Aza treated GalTKO BM-MSCs showed an enhanced demethylation pattern in the second CpG island of the OCT4 promoter region compared to that in the GalTKO BM-MSCs. The exposure of GalTKO pig-derived BM-MSCs to the N2B27-based microenvironment can significantly enhance their trans-differentiation ability into pancreatic β-like cells.

• Journal of Life Science
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• v.16 no.5
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• pp.767-772
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• 2006

This study was to investigate the effect of betaine on the hypoglycemia and hepatoprotection of streptozotocin(STZ)-induced diabetic rats. Male Sprague-Dawley rats weighing around 280 g were randomly assigned to the three experimental groups: a healthy normal group and two groups with STZ-induced diabetes and fed either control diet or betaine diet. Betaine given to the STZ-diabetic rats had significant effect in lowering the serum glucose concentrations compared to the STZ-diabetic rats. The alanine aminotransferase (AST) and aspartate aminotransferase (ALT) activities and triglyceride contents in serum were dramatically higher in the STZ-diabetic rats, but these increases in relation to diabetes also decreased in the STZ-diabetic rats fed betaine. However, the total-cholesterol concentration in the STZ-diabetic rats was even increased by betaine. The morphology of the pancreatic islets in the normal rats showed a typical round form, but most of the islets in the STZ-diabetic rats showed severe morphological alterations by being markedly destroyed. However, the islet morphology of STZ-diabetic rats given betaine mostly maintained a normal rounded appearance. The present study strongly suggests that the administration of betaine showed a moderate hypoglycemic effect by protecting the pancreatic beta-cells by morphological examination from STZ-induced destruction.

• Korean Journal of Pharmacognosy
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• v.30 no.2
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• pp.123-129
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• 1999

The hypoglycemic effect of mulberry leaves using alloxan-induced diabetic mice was investigated. The hypoglycemic effect of mulberry leaves was significantly affected with anaerobic incubation up to for 6 hrs. The body weight of mice treated with 20% anaerobic conditioned mulberry leaves was higher than that in the control group. Mulberry leaves which were treated with anaerobic condition significantly decreased blood glucose level in alloxan-induced type I diabetes mice. Furthermore, glucose tolerance was significantly recovered by feeding mulberry leaves anaerobically treated. Pathological analysis revealed that the disappearance of insulin-secreting beta-cells in the islets of Langerhans from the alloxan induced diabetic mice was strongly inhibited in the mulberry leaves feeding group. The content of 1-deoxynojirimycin increased up to 5% in detached mulberry leaves incubated under nitrogen gas for 6 hrs. Nevertheless, it is not clear whether the synthesis of 1-deoxynojirimycin is increased or the degradation of it is decreased. Overall, results obtained from this study indicate that the hypoglycemic effect was increased by the mulberry leaves with anaerobic treatment.

• Biomolecules & Therapeutics
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• v.28 no.2
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• pp.163-171
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• 2020

Silibinin exhibits antidiabetic potential by preserving the mass and function of pancreatic β-cells through up-regulation of estrogen receptor-α (ERα) expression. However, the underlying protective mechanism of silibinin in pancreatic β-cells is still unclear. In the current study, we sought to determine whether ERα acts as the target of silibinin for the modulation of antioxidative response in pancreatic β-cells under high glucose and high fat conditions. Our in vivo study revealed that a 4-week oral administration of silibinin (100 mg/kg/day) decreased fasting blood glucose with a concurrent increase in levels of serum insulin in high-fat diet/streptozotocin-induced type 2 diabetic rats. Moreover, expression of ERα, NF-E2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) in pancreatic β-cells in pancreatic islets was increased by silibinin treatment. Accordingly, silibinin (10 μM) elevated viability, insulin biosynthesis, and insulin secretion of high glucose/palmitate-treated INS-1 cells accompanied by increased expression of ERα, Nrf2, and HO-1 as well as decreased reactive oxygen species production in vitro. Treatment using an ERα antagonist (MPP) in INS-1 cells or silencing ERα expression in INS-1 and NIT-1 cells with siRNA abolished the protective effects of silibinin. Our study suggests that silibinin activates the Nrf2-antioxidative pathways in pancreatic β-cells through regulation of ERα expression.

• Nutrition Research and Practice
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• v.7 no.2
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• pp.103-108
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• 2013

A folk prescription consisting of Alnus hirsuta, Rosa davurica, Acanthopanax senticosus and Panax schinseng has been used in the treatment of diabetes mellitus. The aim of the present investigation was to evaluate the antidiabetic effects of the herb formula extract (HFE) composed of Alnus hirsuta, Rosa davurica, Acanthopanax senticosus and Panax schinseng in the streptozotocin (STZ)-induced diabetic rats. The HFE was mixed in the food supply of the healthy and STZ-induced diabetic male Sprague-Dawley rats, and its effects on the body weight, water and food intake, hyperglycemia, hypolipidemic and islet structure were studied. The treatment of the rats with STZ for 6 weeks resulted in marasmus, polydipsia, polyphagia, hyperglycemia and hypoinsulinemia. In addition, the diabetic rats showed an apparent decrease in the insulin immunoreactivity and the number of ${\beta}$-cells in the pancreas. The addition of the HFE to the rats' food supply significantly lowered the serum glucose and the serum triglycerides level and preserved the normal histological appearance of the pancreatic islets. These results indicate that the HEF have a strong antidiabetic potential along with the significant hypoglycemic and hypolipidemic effects, which may be applicable in the pharmaceutical industry.

• Biomolecules & Therapeutics
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• v.26 no.2
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• pp.201-209
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• 2018

G protein-coupled receptor 119 (GPR119) is expressed in the pancreas and gastrointestinal tract, and its activation promotes insulin secretion in the beta cells of the pancreatic islets as well as the secretion of glucagon-like peptide-1 (GLP-1) in intestinal L cells, consequently improving glucose-stimulated insulin secretion. Due to this dual mechanism of action, the development of small-molecule GPR119 agonists has received significant interest for the treatment of type 2 diabetes. We newly synthesized 1,2,4-triazolone derivatives of GPR119 agonists, which demonstrated excellent outcomes in a cyclic adenosine monophosphate (cAMP) assay. Among the synthesized derivatives, YH18968 showed cAMP=2.8 nM; in GLUTag cell, GLP-1secretion=2.3 fold; in the HIT-T15 cell, and insulin secretion=1.9 fold. Single oral administration of YH18968 improved glucose tolerance and combined treatment with a dipeptidyl peptidase 4 (DPP-4) inhibitor augmented the glucose lowering effect as well as the plasma level of active GLP-1 in normal mice. Single oral administration of YH18968 improved glucose tolerance in a diet induced obese mice model. This effect was maintained after repeated dosing for 4 weeks. The results indicate that YH18968 combined with a DPP-4 inhibitor may be an effective therapeutic candidate for the treatment of type 2 diabetes.